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Understanding Diseases “Cancer is fundamentally a disease of failure of regulation of tissue growth. In order for a normal cell to transform into a cancer cell, the genes which regulate cell growth and differentiation must be altered.” – from Wikipedia Research on cell differentiation helps understanding diseases such as cancer. 8

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C. elegans: A Model Organism Earthworm used in developmental biology. 959 cells; its organs found in other animals. Differentiation studied on vulval development. 9

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Differentiation and then development into organ parts 10 Initial division of embryo Identical precursor cells collaborate to decide their fate

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Modeling Goal 11 What is the mechanism (program) within each cell for deciding fates through communication?

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Building Blocks of these Programs Cells contain communicating proteins. Protein interaction: a protein senses the concentration of other proteins. Interaction is either activation or inhibition. 12 A B A B

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Additional Algorithms for Going Beyond Synthesis to Assist Scientists 29 Does there exist alternative model that differs on new experiment? For two or more models within the space, do there exist disambiguating experiments? What are the minimal number of experiments that constrain the space to current model?

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Crux of the research problem Intelligent rule instantiation: ------ edges Given target chemical Phrase it as a model checking reachability problem: initial experiments point to a need for more efficient representation of search space. Need better search methods